Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus

Most influenza viruses express the PB1-F2 protein which is regarded as a virulence factor. However, PB1-F2 behaves differently in avian and mammalian hosts, suggesting that this protein may be involved in the species barrier crossings regularly observed in influenza viruses. To better understand the...

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Main Authors: Joëlle Mettier, Clémentine Prompt, Elise Bruder, Bruno Da Costa, Christophe Chevalier, Ronan Le Goffic
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/2/328
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author Joëlle Mettier
Clémentine Prompt
Elise Bruder
Bruno Da Costa
Christophe Chevalier
Ronan Le Goffic
author_facet Joëlle Mettier
Clémentine Prompt
Elise Bruder
Bruno Da Costa
Christophe Chevalier
Ronan Le Goffic
author_sort Joëlle Mettier
collection DOAJ
description Most influenza viruses express the PB1-F2 protein which is regarded as a virulence factor. However, PB1-F2 behaves differently in avian and mammalian hosts, suggesting that this protein may be involved in the species barrier crossings regularly observed in influenza viruses. To better understand the functions associated with this viral protein, we decided to compare the BioID2-derived proximity interactome of a human PB1-F2 from an H3N2 virus with that of an avian PB1-F2 from an H7N1 strain. The results obtained reveal that the two proteins share only a few interactors and thus common functions. The human virus protein is mainly involved in signaling by Rho GTPases while the avian virus protein is mainly involved in ribonucleoprotein complex biogenesis. PB1-F2 H3N2 interactors include several members of the 14-3-3 protein family, a family of regulatory proteins involved in many signaling pathways. We then validated the interaction with 14-3-3 proteins and were able to show that the association of H3N2-PB1-F2 with YWHAH increased the activity of the antiviral sensor MDA5, while H7N1-PB1-F2 had no effect. Collectively, these results show that PB1-F2 can associate with a large range of protein complexes and exert a wide variety of functions. Furthermore, PB1-F2 interactome differs according to the avian or human origin of the protein.
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spelling doaj.art-3bc8c80f94b44027be9748365b2689852023-11-16T23:47:31ZengMDPI AGViruses1999-49152023-01-0115232810.3390/v15020328Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza VirusJoëlle Mettier0Clémentine Prompt1Elise Bruder2Bruno Da Costa3Christophe Chevalier4Ronan Le Goffic5INRAE, UVSQ, UMR892 VIM, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceINRAE, UVSQ, UMR892 VIM, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceINRAE, UVSQ, UMR892 VIM, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceINRAE, UVSQ, UMR892 VIM, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceINRAE, UVSQ, UMR892 VIM, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceINRAE, UVSQ, UMR892 VIM, Université Paris-Saclay, 78350 Jouy-en-Josas, FranceMost influenza viruses express the PB1-F2 protein which is regarded as a virulence factor. However, PB1-F2 behaves differently in avian and mammalian hosts, suggesting that this protein may be involved in the species barrier crossings regularly observed in influenza viruses. To better understand the functions associated with this viral protein, we decided to compare the BioID2-derived proximity interactome of a human PB1-F2 from an H3N2 virus with that of an avian PB1-F2 from an H7N1 strain. The results obtained reveal that the two proteins share only a few interactors and thus common functions. The human virus protein is mainly involved in signaling by Rho GTPases while the avian virus protein is mainly involved in ribonucleoprotein complex biogenesis. PB1-F2 H3N2 interactors include several members of the 14-3-3 protein family, a family of regulatory proteins involved in many signaling pathways. We then validated the interaction with 14-3-3 proteins and were able to show that the association of H3N2-PB1-F2 with YWHAH increased the activity of the antiviral sensor MDA5, while H7N1-PB1-F2 had no effect. Collectively, these results show that PB1-F2 can associate with a large range of protein complexes and exert a wide variety of functions. Furthermore, PB1-F2 interactome differs according to the avian or human origin of the protein.https://www.mdpi.com/1999-4915/15/2/328influenza virusPB1-F2BioID2interactomevirulence factor14-3-3 proteins
spellingShingle Joëlle Mettier
Clémentine Prompt
Elise Bruder
Bruno Da Costa
Christophe Chevalier
Ronan Le Goffic
Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus
Viruses
influenza virus
PB1-F2
BioID2
interactome
virulence factor
14-3-3 proteins
title Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus
title_full Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus
title_fullStr Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus
title_full_unstemmed Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus
title_short Comparison of PB1-F2 Proximity Interactomes Reveals Functional Differences between a Human and an Avian Influenza Virus
title_sort comparison of pb1 f2 proximity interactomes reveals functional differences between a human and an avian influenza virus
topic influenza virus
PB1-F2
BioID2
interactome
virulence factor
14-3-3 proteins
url https://www.mdpi.com/1999-4915/15/2/328
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